1-[2-(3-hydroxyadamant-1-yl-amino)acetyl]pyrrolidin-(2S)-carbonitrile of the formula

(INN: vildagliptin) is used for the treatment of type 2 diabetes (non-insulin dependent). It is known that dipeptidile peptidase IV (DPP-IV) inhibitors are effective in the treatment of diseases which are mediated by DPP-IV. DPP-IV inhibits glucagon-like peptide-1 (GLP-1), which is one of the main stimulants of insulin secretion of pancreas. Moreover GLP-1 positively influences glucose transformation. Therefore inhibition of DPP-IV is effective in the treatment of diseases such as non-insulin dependent diabetes mellitus (NIDDM).
1-[2-(3-hydroxyadamant-1-yl-amino)acetyl]pyrrolidin-(2S)-carbonitrile of formula I (vildagliptin) and the pharmaceutically acceptable salts thereof are described first in EP 1 137 635 A1. Vildagliptin base and some analogues therefore are described in EP 1 137 635 A1 and pharmaceutical acceptable acid addition salts thereof are generally mentioned in the specification.
WO 2007/019255 international patent application describes pharmaceutically acceptable acid addition salts of vildagliptin. Five of the salts, such as hydrochloride, hydrogen sulphate (two polymorphs) hydrogen fumarate, hydrogen malonate are characterised by physical and spectral data.
It is known, that the solubility and bioavailability of the bases are not always sufficient. Therefore the stabilization by salt formation could be a useful solution.
According to WO 2007019255 the salts of vildagliptin—stored in solid form or in the organism—are more stable than the vildagliptin base of formula I. The salts are more soluble in water, therefore they have potentially better bioavailability. According to the description of WO 2007019255 the salts are not hygroscopic and have advantageous formulation properties. The application compares the stability of the vildagliptin base, hydrochloride and hydrogen fumarate salts mixed with several excipients under different conditions. According to the results the stability of the salts is better than that of the base in powder mixture. In pages 44 to 45 of WO 2007019255 it is described that vildagliptin base almost completely decomposes in water until three days and only 7.5% active ingredient is detectable after tree days contrary to the salts.
Physical and chemical properties and spectral data of vildagliptin polymorphisms are not known.